P357: DECITABINE CONSOLIDATION AFTER CD19/CD22 CAR-T THERAPY IS A NOVEL STRATEGY TO IMPROVE OUTCOMES IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Tingting LI, Qingya Cui, Sining Liu, Zheng LI, Wei Cui, Mengyun LI, Xiaming Zhu, Liqing Kang, Lei Yu, Depei Wu, Xiaowen Tang
Journal: HemaSphere (2023)

Background: Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, approximately 50% of patients who achieved complete remission (CR) after CAR-T cell therapy experienced relapse within one year, and there was no recommended maintenance therapy at present. Decitabine (DAC) has been proven to block DNA methylation, inhibit T cell exhaustion, and modulate the tumor microenvironment. Studies have shown that low-dose DAC pretreatment of CAR-T cells significantly improves the phenotype and function of CAR-T cells and enhances the anti-leukemic effect of CART cells. Whether DAC consolidation given after CAR-T treatment can improve the efficacy and reduce the relapse rate in r/r B-ALL? Therefore, we evaluated the efficacy of DAC consolidation followed by CD19/CD22 CAR-T treatment in patients with r/r B-ALL. Aims: To evaluate the efficacy of DAC consolidation after treatment with CD19/CD22 CAR-T for r/r B-ALL. Methods: We retrospectively analyzed 48 patients with r/r B-ALL treated with CD19/CD22 CAR-T cells, 16 of whom received DAC consolidation (20 mg/m2/day for 5 days at 6-week intervals) after CAR-T cell therapy (DAC group) and 32 patients without DAC consolidation (CON group). Results: There were no significant differences in baseline characteristics between the two groups except for alterations in TP53. Six patients (37.5%) in the DAC group had TP53 mutations, while none in the CON group (p=0.001). The day 28 after CD19/CD22 CAR-T infusion, all patients achieved CR or CR with incomplete hematologic recovery, with 14 (87.5%) patients in the DAC group achieving minimal residual disease (MRD) negative CR compared with 29 (90.6%) in the CON group. However, there was a significant difference in overall survival (OS) of DAC and CON group: the 3-year OS rates were 90.9% versus 66.1% (P=0.039) (Figure 1A), with median OS of 30.28 months and 21.4 months, respectively. The 3-year leukemia-free survival (LFS) rates for both groups were 81.3% versus 61.3% (P=0.272), with median LFS of 27.78 months and 20.74 months, respectively. Within one year of CAR-T treatment, there were 2 relapses in the DAC group (12.5%) and 8 relapses in the CON group (25%), and the 3-year cumulative incidence of relapse between DAC and CON group were 18.7% and 38.7%. In the subgroup analysis, patients in relapse status prior to CD19/CD22 CAR-T therapy benefited from DAC consolidation, with 3-year OS of 100% versus 66.2% (P=0.048), respectively. Patients who did not bridge hematopoietic stem cell transplantation (HSCT) followed by CD19/CD22 CAR-T treatment also benefited from DAC consolidation, with 3-year OS of 100% versus 48% (P=0.064)(Figure 1B). Summary/Conclusion: Our retrospective study showed that DAC consolidation after CD19/CD22 CAR-T therapy was a novel maintenance strategy to improve the prognosis of r/r B-ALL patients.Keywords: CAR-T, B cell acute lymphoblastic leukemia, Consolidation, decitabine